Table 1.

Examples of drugs well suited for Tier B versus C development

Attribute	Tier B	Tier C
Example spectrum	Broad with MDR pathogen coverage	Narrow MDR pathogen coverage
Example target pathogen	MDR Enterobacteriaceae (also covers if non-MDR)	Pseudomonas aeruginosa only
Challenge in studying the MDR pathogen in large numbers?	Yes	Yes
Detailed insight into:
Microbiology including mechanism of action and resistance?	Yes	Yes
Animal models that mimic human disease?	Yes	Yes
Exposure response in animals?	Yes	Yes
Detailed PK–PD justification of dose selection in humansa	Yes	Yes
Can do “standard” P3 study versus susceptible organisms?	Yesb	No
Randomized comparative data generated?	Yes (single body site, vs. standard comparator)	Yes (multiple body sites, vs. BATc)
Able to do “usual strength” statistical inference testing?	Yes, but only in the standard P3 study	No
Pooling of data across infection sites proposed?	Yes	Yes
Reliance on a totality-of-evidence approach?d	High	Even higher

MDR, multidrug resistant.

^aThe mechanism of action is understood, animal models are available that reasonably mimic human disease at relevant sites, an exposure–response relationship in the animal studies informs human dose with an adequate safety margin, and PK is known in healthy volunteers and relevant patient groups.

^bThis provides relevant efficacy data if MDR pathogens have same susceptibility to a new agent as do non-MDR pathogens.

^cBAT, best available therapy, standardized insofar as possible.

^dAll drug reviews consider the totality of evidence, but the reliance on such things as PK–PD predictions and pooled responses across sites will be very high here.